Pik3ca gene

Author: Prof. Dr. med. Peter Altmeyer

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Last updated on: 20.07.2021

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Synonym(s)

OMIM:171834; Phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha; Phosphoinositide-3-kinase, catalytic, alpha polypeptides

Definition
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PIK3CA is the acronym for phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha.

Phosphoinositide 3-kinases also known as PI-3-kinases (PI3K), are one of the most frequently dysregulated signaling pathways in human cancers and are associated with many cellular functions such as cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. PIK3CA is an integral component of the PI3K signaling pathway. PIK3CA has long been described as an oncogene. The kinase has two major hotspots for activating mutations, the 542/545 region of the helical domain and the 1047 region of the kinase domain. A pseudogene of this gene has been defined on chromosome 22.

Determination of the mutation status of the PIK3CA gene is important, among other things, in the treatment of patients with:

Classification
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List of diseases with proven germ line and somatic mutations in the PIK3CA gene:

  • Pathogenic germline mutation(s): Cowden syndrome
  • Somatic mutation(s) causing the disease: CLOVE(S) syndrome
  • Disease-causing somatic mutation(s): Hemihyperplasia-multiple lipomatosis syndrome
  • Somatic mutation(s) causing the disease: Hemimegalencephaly
  • Disease-causing somatic mutation(s): Hepatocellular carcinoma, adult
  • Disease-causing somatic mutation(s): Macrodactyly of the fingers, unilateral
  • Disease-causing somatic mutation(s): macrodactyly of the toes, unilateral hemihyperplasia-multiple lipomatosis syndrome
  • Disease-causing somatic mutation(s): Segmental-progressive large growth syndrome with fibroadipose hyperplasia

General information
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The mutation frequency of PIK3CA is approximately 30% in breast carcinoma, 10-30% in colorectal carcinoma and 1-3% in lung carcinoma . In non-small cell lung cancer(NSCLC), PIK3CA mutations can occur together with mutations in the EGFR gene.

Etiology
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Under consumption of ATP, phosphatidylinositiol, phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bisphosphate are phosphorylated to produce PIP3 (phosphatidylinositol-3,4,5-trisphosphates). PIP3 plays a key role in the activation of signalling cascades involved in cell growth, survival, proliferation, motility and morphology.

Note(s)
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PIK3CA inhibitors for solid tumours are currently still in clinical development.

Literature
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Last updated on: 20.07.2021